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Development of a nano-emulsion based multivalent protein subunit vaccine against Pseudomonas aeruginosa
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Issue Date
2024-04-18Author
Howlader, Debaki R.
Mandal, Rahul Shubhra
Lu, Ti
Maiti, Suhrid
Dietz, Zackary K.
Das, Sayan
Whittier, Sean K.
Nagel, Aaron C.
Biswas, Satabdi
Varisco, David J.
Gardner, Francesca M.
Ernst, Robert K.
Picking, William D.
Picking, Wendy L.
Publisher
Frontiers Media
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
Copyright © 2024 Howlader, Mandal, Lu, Maiti, Dietz, Das, Whittier, Nagel, Biswas, Varisco, Gardner, Ernst, Picking and Picking
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Show full item recordAbstract
Pseudomonas aeruginosa (Pa) is an opportunistic bacterial pathogen responsible for severe hospital acquired infections in immunocompromised and elderly individuals. Emergence of increasingly drug resistant strains and the absence of a broad-spectrum prophylactic vaccine against both T3SA+ (type III secretion apparatus) and ExlA+/T3SA- Pa strains worsen the situation in a post-pandemic world. Thus, we formulated a candidate subunit vaccine (called ExlA/L-PaF/BECC/ME) against both Pa types. This bivalent vaccine was generated by combining the C-terminal active moiety of exolysin A (ExlA) produced by non-T3SA Pa strains with our T3SA-based vaccine platform, L-PaF, in an oil-in-water emulsion. The ExlA/L-PaF in ME (MedImmune emulsion) was then mixed with BECC438b, an engineered lipid A analogue and a TLR4 agonist. This formulation was administered intranasally (IN) to young and elderly mice to determine its potency across a diverse age-range. The elderly mice were used to mimic the infection seen in elderly humans, who are more susceptible to serious Pa disease compared to their young adult counterparts. After Pa infection, mice immunized with ExlA/L-PaF/BECC/ME displayed a T cell-mediated adaptive response while PBS-vaccinated mice experienced a rapid onset inflammatory response. Important genes and pathways were observed, which give rise to an anti-Pa immune response. Thus, this vaccine has the potential to protect aged individuals in our population from serious Pa infection.
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Citation
Howlader DR, Mandal RS, Lu T, Maiti S, Dietz ZK, Das S, Whittier SK, Nagel AC, Biswas S, Varisco DJ, Gardner FM, Ernst RK, Picking WD, Picking WL. Development of a nano-emulsion based multivalent protein subunit vaccine against Pseudomonas aeruginosa. Front Immunol. 2024 Apr 18;15:1372349. doi: 10.3389/fimmu.2024.1372349. PMID: 38698863; PMCID: PMC11063228
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